Low susceptibility of NC/Nga mice to tumor necrosis factor-alpha-mediated lethality and hepatocellular damage with D-galactosamine sensitization.
The susceptibility of NC/Nga mice to tumor necrosis factor (TNF)-alpha was examined by using sensitization with d-galactosamine (d-GalN). Administration of TNF-alpha and d-GalN killed none of the NC/Nga mice, whereas it killed all of the BALB/c mice. Treatment with TNF-alpha and d-GalN caused few hepatic lesions in NC/Nga mice but massive hepatocellular apoptosis in BALB/c mice. Unlike BALB/c mice, there was no elevation in caspase 3 and 8 activities in the livers of NC/Nga mice receiving TNF-alpha and d-GalN. On the other hand, administration of anti-Fas antibody definitely killed both NC/Nga and BALB/c mice via activation of caspases 3 and 8. Treatment with TNF-alpha and d-GalN led to translocation of nuclear factor (NF)-kappaB in NC/Nga and BALB/c mice. However, NF-kappaB translocation was sustained in NC/Nga mice, although it disappeared in BALB/c mice 7 h after the treatment. NF-kappaB inhibitors activated caspases 3 and 8, and enhanced TNF-alpha-mediated lethality in NC/Nga. Taken together, the low susceptibility of NC/Nga mice to TNF-alpha-mediated lethality was suggested to be responsible for the sustained NF-kappaB activation.
Koide
Naoki
N
Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan. koide@aichi-med-u.ac.jp
Morikawa
Akiko
A
Naiki
Yoshikazu
Y
Tumurkhuu
Gantsetseg
G
Yoshida
Tomoaki
T
Ikeda
Hiroshi
H
Yokochi
Takashi
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D058846:Antibodies, Monoclonal, Murine-Derived; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D005688:Galactosamine / Q000276:immunology / Q000633:toxicity*; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D016328:NF-kappa B / Q000378:metabolism*; D011994:Recombinant Proteins / Q000633:toxicity; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000633:toxicity*; D019014:fas Receptor / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; C491899:Fas protein, mouse; D016328:NF-kappa B; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C411023:anti-Fas monoclonal antibody; D019014:fas Receptor; D005688:Galactosamine; D053148:Caspase 3; D053181:Caspase 8